FDA Approves Combo Drug for HF in Blacks

The controversy over the impact of a race-based HF indication were expressed by speakers during the open public hearing. None opposed the drug's approval, but several argued against approving it specifically for black patients.

Charles Rotini, Ph.D., of the National Human Genome Center at Howard University, Washington, said that group identity is confused with ancestry, and that African Americans have a diverse ancestry. He said it would be tragic not to approve the drug, but “just as tragic” to approve it for the black population only.

Charles Curry, M.D., president of the International Society on Hypertension in Blacks and former chief of cardiology at Howard University, said he “vigorously” supported approval and called BiDil “the most important advance in the care of black people we have seen in my lifetime.” But he also expressed concern about limiting a life-saving treatment to one group of patients, noting that early trials were conducted almost exclusively in white men, but have benefited all populations.

“Would anyone restrict the results of 4S [Scandinavian Simvastatin Survival Study] to Scandinavians?” asked Dr. Curry who, as an A-HeFT investigator and member of the trial's cosponsor, the Association of Black Cardiologists, received funds from NitroMed.

Those expressing unconditional support for the approval included the chair of the Congressional Black Caucus and representatives of the National Minority Health Month Foundation and the NAACP.

In A-HeFT, headache, dizziness, and hypotension were higher in the BiDil patients, and worsening of HF was more common in the placebo patients. Arthralgias were reported in 1.5% of those on BiDil, vs. 0.4% of those on placebo, about a fourfold greater rate that falls “into a category of some concern” about the potential for a drug-induced lupus-like syndrome that has been associated with hydralazine, said Jonathan Sackner-Bernstein, M.D., director of the HF program at St. Luke's-Roosevelt Hospital Center, New York, noting that such events could be monitored after approval.

Jay N. Cohn, M.D., was principal investigator of V-HeFT I, which compared the drug combination with placebo added to standard therapy in the early 1980s in male patients with mild HF, and a few years later, V-HeFT II, which compared the combination with enalapril, added to standard therapy. The results suggested benefits, but were not adequate for FDA approval.

In a retrospective analysis, Dr. Cohn found that benefit seemed more favorable in black patients, which, after discussions with the FDA, led to the A-HeFT trial. The FDA said a single positive study in an HF population could be the basis for approval as a treatment for HF in black patients, and the trial began in May 2001. Dr. Cohn, the inventor of BiDil, holds equity in and stands to receive royalties from the sale of BiDil.

The findings confirmed the hypotheses generated from V-HeFT I and II, said Clyde Yancy, M.D., medical director of the Heart Failure/Transplantation Program at the University of Texas Southwestern Medical School, Dallas, speaking for NitroMed. The black population has a high rate of HF, which appears at a younger age, often with greater left ventricular dysfunction and a less favorable prognosis, he noted.

The BiDil application may not be so precedent setting as has been portrayed, Dr. Nissen said, citing the recent approval of the fixed-dose combination of losartan and hydrochlorothiazide for reducing the stroke risk in patients with hypertension and left ventricular hypertrophy, with a label that says evidence suggests this benefit does not apply to black patients.

Dr. Charles Curry lauded BiDil as an unparalleled advance for black people. James Reinaker